A Review of Phenytoin Monotherapy in Adults With Nonrefractory Status Epilepticus

Objective: To review the literature evaluating the efficacy of phenytoin monotherapy in adults with nonrefractory status epilepticus. Data Sources: Articles were selected through a search of MEDLINE/PubMed (1966 to August 2014), using the terms phenytoin and status epilepticus. A further review of reference citations was performed to identify other relevant articles. Study Selection and Data Extraction: English-language case reports and clinical studies were reviewed. Publications evaluating the efficacy of phenytoin monotherapy primarily in adults with nonrefractory status epilepticus were included in the review. Two case studies and 5 clinical studies met the criteria. Data Synthesis: The ultimate goal for status epilepticus treatment is seizure cessation. Phenytoin, a venerable and oft-utilized antiepileptic, has been employed in first-line and second-line regimens for status epilepticus. Unfortunately, despite decades of use, data on the efficacy of phenytoin monotherapy in these nonrefractory cases have been limited. The available studies are quite heterogeneous in design, with variable underlying etiologies of status epilepticus, doses of study drugs, and comparators. Additionally, most are underpowered. When administered as second-line therapy, phenytoin monotherapy is comparable to valproic acid in abating status epilepticus. As first-line therapy, phenytoin monotherapy was inferior to lorazepam but not diazepam when used in combination with phenytoin or phenobarbital. Two other studies comparing phenytoin with valproic acid as first-line therapy had conflicting results. Conclusions: In adults with nonrefractory status epilepticus, phenytoin monotherapy is a viable option for second-line therapy. The data do not consistently support phenytoin monotherapy's use as first-line treatment. More robust and adequately powered clinical studies are needed to assess whether these results remain consistent and extend to more long-term efficacy measures, such as morbidity and mortality.